Histone modifications are implicated in influencing gene expression. To map the human epigenomes at high resolution, we have developed a technique termed ChIP-Seq by combining the chromatin immunoprecipitation assays (ChIP) with the Solexa 1G high throughput sequencing technology. We have generated high-resolution maps for the genome-wide distribution of 40 histone lysine and arginine methylations as well as histone variant H2A.Z, RNA polymerase II and the insulator binding protein CTCF across the human genome using ChIP-Seq. We have also mapped genome-wide nucleosome positions in resting and activated human T cells. Using these, we have analyzed the patterns of histone modifications in regulatory regions including promtoers and enhancers. Our data indicate that multiple modifications function together to define chromatin structure required for gene regulation. Our data provide new insights into the function of histone modifications and chromatin organization in genome function.